More drugs being approved for rare diseases in kids

NEW YORK (Reuters Health) - A growing number of drugs are coming to market to help treat rare diseases in children, a new U.S. government study finds.

Officials say the findings, reported in the journal Pediatrics, suggest that a U.S. law known as the Orphan Drug Act is working as intended.

"Orphan" drugs are called that because they target uncommon diseases that have traditionally been neglected by drug companies -- since developing treatments for rare conditions is a generally unprofitable endeavor.

The Orphan Drug Act was passed in 1983 to offer companies tax credits, marketing rights and other incentives to focus on rare diseases.

In the new study, officials at the U.S. Food and Drug Administration (FDA) found that between 2000 and 2009, there were more than three dozen orphan drug approvals for rare disorders affecting children and teenagers.

And pediatric diseases are accounting for a growing proportion of those approvals.

In the first half of the 2000-2009 decade, just 10 of 57 orphan drug approvals were for pediatric conditions. In the latter half, that rose to 28 of 91, the FDA found.

In all, there were 38 approvals for rare pediatric conditions -- though that sometimes meant a single drug got several approvals for different uses.

Disorders affecting the hormonal and metabolic systems accounted for the biggest share of approvals (39 percent).

For example, somatropin -- a synthetic form of human growth hormone -- won several different approvals over the decade. The drug got the OK to treat short stature and growth failure due to small birth size and certain rare genetic conditions, like Prader-Willi syndrome and Noonan syndrome.

The researchers also found that the most-rare conditions benefited the most: More than half of new approvals were for the least common disorders -- those affecting fewer than 20,000 Americans.

That's something of a "pleasant surprise," since drug companies stand to make the least profit from treating "ultra-rare" diseases, according to senior researcher Dr. Menfo A. Imoisili, of the FDA.

While the findings are encouraging, the study looked only at numbers, noted a researcher not involved in the work.

"They're not looking at the quality of the approved drugs," said Dr. Aaron S. Kesselheim, who researches health policy at the Harvard School of Public Health in Boston.

And there have been concerns raised about the effectiveness and safety of certain orphan drugs on the market.

In a study published last year, Kesselheim found that, at least when it comes to cancer treatments, orphan drugs tend to be approved based on weaker evidence compared with regular drugs.

Clinical trials of orphan drugs are generally small -- by necessity since they are focusing on a rare disease.

But, Kesselheim said, his study found that the trials often have other flaws in their design. In some, for example, the researchers and patients were not "blinded" as to which patients were actually receiving the drug under study -- a step that's considered necessary to keeping investigators' and patients' objectivity.

Only two of the approvals for pediatric conditions between 2000 and 2009 were related to cancer.

But somatropin, for one, has had its own brush with controversy. A 2010 French study found that certain children on the hormone had a small, but higher-than-normal risk of death.

In its own review of that study, the FDA said it found "design weaknesses that limit the interpretability of the study results." The agency says it's still monitoring the issue, and expects to get additional data from the French study this spring.

In Kesselheim's view, orphan drugs, in general, may need closer monitoring after approval. "These kinds of drugs could be subject to greater post-market scrutiny," he told Reuters Health.

In an email, Imoisili agreed that orphan drugs' effects need to be followed after they hit the market.

"There remains a need to maintain vigilance on the post-marketing safety and effectiveness information related to these medications in the 'real world,' if and when they arise," he said.

Kesselheim said that officials might also want to consider whether a particular rare disease already has treatments available. If it does, then there may be less urgency to approve an orphan drug based on lesser-quality evidence.

An estimated 25 million Americans suffer from any of 6,000-plus rare diseases -- "rare" being defined as affecting fewer than 200,000 people nationwide. In Europe, where regulators have taken similar actions to boost orphan drug development, a rare disease is one that affects fewer than five in 10,000 people. About 30 million Europeans suffer from those conditions.